Neurofilament proteins and cAMP pathway in brains of μ-, δ- or κ-opioid receptor gene knock-out mice: effects of chronic morphine administration

2004 ◽  
Vol 46 (4) ◽  
pp. 519-530 ◽  
Author(s):  
J.A. Garcı́a-Sevilla ◽  
M. Ferrer-Alcón ◽  
M. Martín ◽  
B.L. Kieffer ◽  
R. Maldonado
Keyword(s):  
Opioid Receptor ◽  
Receptor Gene ◽  
Neurofilament Proteins ◽  
Chronic Morphine ◽  
Knock Out ◽  
Camp Pathway ◽  
Morphine Administration ◽  
Knock Out Mice

scholarly journals Transcriptional Regulation of Mouse μ Opioid Receptor Gene by PU.1

2004 ◽  
Vol 279 (19) ◽  
pp. 19764-19774 ◽  
Author(s):  
Cheol Kyu Hwang ◽  
Chun Sung Kim ◽  
Hack Sun Choi ◽  
Scott R. McKercher ◽  
Horace H. Loh
Keyword(s):  
Transcription Factors ◽  
Opioid Receptor ◽  
Trichostatin A ◽  
Receptor Gene ◽  
Hematopoietic Cells ◽  
Mobility Shift ◽  
Knock Out ◽  
Cis Acting ◽  
Μ Opioid Receptor ◽  
Mobility Shift Assay

We previously reported that the 34-bp cis-acting element of the mouse μ opioid receptor (MOR) gene represses transcription of the MOR gene from the distal promoter. Using a yeast one-hybrid screen to identify potential transcription factors of the MOR promoter, we have identified PU.1 as one of the candidate genes. PU.1 is a member of theetsfamily of transcription factors, expressed predominantly in hematopoietic cells and microglia of brain. PU.1 plays an essential role in the development of both lymphoid and myeloid lineages. Opioids exert neuromodulatory as well as immunomodulatory effects, which are transduced by MOR. Moreover, MOR-deficient mice exhibit increased proliferation of hematopoietic cells, suggesting a possible link between the opioid system and hematopoietic development. The PU.1 protein binds to the 34-bp element of the MOR gene in a sequence-specific manner confirmed by electrophoretic mobility shift assay and supershift assays. We have also determined endogenous PU.1 interactions with the 34-bp element of MOR promoter by chromatin immunoprecipitation assays. In co-transfection studies PU.1 represses MOR promoter reporter constructs through its PU.1 binding site. When the PU.1 gene is disrupted as in PU.1 knock-out mice and using small interfering RNA-based strategy in RAW264.7 cells, the transcription of the endogenous target MOR gene is increased significantly. This increase is probably mediated through modification of the chromatin structure, as suggested by the reversal of the PU.1-mediated repression of MOR promoter activity after trichostatin A treatment in neuroblastoma NMB cells. Our results suggest that PU.1 may be an important regulator of the MOR gene, particularly in brain and immune cells.

scholarly journals Mu opioid receptor and orexin/hypocretin mRNA levels in the lateral hypothalamus and striatum are enhanced by morphine withdrawal

2006 ◽  
Vol 191 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Yan Zhou ◽  
Jacob Bendor ◽  
Lauren Hofmann ◽  
Matthew Randesi ◽  
Ann Ho ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Lateral Hypothalamus ◽  
Brain Regions ◽  
Mu Opioid Receptor ◽  
Morphine Withdrawal ◽  
Mrna Levels ◽  
Chronic Morphine ◽  
Mu Opioid ◽  
Morphine Administration ◽  
Related Stress

In this study, we investigated the effects of acute morphine administration, chronic intermittent escalating-dose morphine administration and spontaneous withdrawal from chronic morphine on mRNA levels of mu opioid receptor (MOP-r), and the opioid peptides pro-opiomelanocortin (POMC) and preprodynorphin (ppDyn) in several key brain regions of the rat, associated with drug reward and motivated behaviors: lateral hypothalamus (lat.hyp), nucleus accumbens (NAc) core, amygdala, and caudate–putamen (CPu). There was no effect on MOP-r mRNA levels in these brain regions 30 min after either a single injection of morphine (10 mg/kg, i.p.) or chronic intermittent escalating-dose morphine (from 7.5 mg/kg per day on day 1 up to 120 mg/kg per day on day 10). Activation of the stress-responsive hypothalamic–pituitary–adrenal axis by 12 h withdrawal from chronic morphine was confirmed; both POMC mRNA levels in the anterior pituitary and plasma adrenocorticotropic hormone levels were significantly elevated. Under this withdrawal-related stress condition, there was an increase in MOP-r mRNA levels in the lat.hyp, NAc core, and CPu. Recent studies have demonstrated a novel role for the lat.hyp orexin (or hypocretin) activation in both drug-related positive rewarding, and withdrawal effects. Around 50% of lat.hyp orexin neurons express MOP-r. Therefore, we also examined the levels of lat.hyp orexin mRNA, and found them increased in morphine withdrawal, whereas there was no change in levels of the lat.hyp ppDyn mRNA, a gene coexpressed with the lat.hyp orexin. Our results show that there is an increase in MOP-r gene expression in a region-specific manner during morphine withdrawal, and support the hypothesis that increased lat.hyp orexin activity plays a role in morphine-withdrawal-related behaviors.

scholarly journals Regulation of δ-Opioid Receptor Trafficking via μ-Opioid Receptor Stimulation: Evidence from μ-Opioid Receptor Knock-Out Mice

2003 ◽  
Vol 23 (12) ◽  
pp. 4888-4898 ◽  
Author(s):  
Anne Morinville ◽  
Catherine M. Cahill ◽  
M. James Esdaile ◽  
Haneen Aibak ◽  
Brian Collier ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Trafficking ◽  
Receptor Stimulation ◽  
Knock Out ◽  
Μ Opioid Receptor ◽  
Knock Out Mice ◽  
Δ Opioid Receptor

scholarly journals Antipruritic Effect of Nalbuphine, a Kappa Opioid Receptor Agonist, in Mice: A Pan Antipruritic

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5517
Author(s):  
Saadet Inan ◽  
Nae Dun ◽  
Alan Cowan
Keyword(s):  
Opioid Receptor ◽  
Skin Diseases ◽  
Kappa Opioid Receptor ◽  
Dependent Manner ◽  
Kappa Opioid ◽  
Knock Out ◽  
Chronic Itch ◽  
The Usa ◽  
Knock Out Mice ◽  
Hiv 1

Antipruritic effects of kappa opioid receptor (KOR) agonists have been shown in rodent models of acute and chronic scratching (itchlike behavior). Three KOR agonists, nalfurafine, difelikefalin, and nalbuphine, are in clinical studies for antipruritic effects in chronic itch of systemic and skin diseases. Nalfurafine (in Japan) and difelikefalin (in the USA) were approved to be used in the treatment of chronic itch in hemodialysis patients. The FDA-approved nalbuphine has been used in clinic for over 40 years, and it is the only narcotic agonist that is not scheduled. We aimed to study (a) antiscratch activity of nalbuphine against TAT-HIV-1 protein (controls HIV transcription)-, deoxycholic acid (DCA, bile acid)-, and chloroquine (CQ)-induced scratching in a mouse model of acute itch; and (b) whether the effect of nalbuphine is produced via KORs. First, dose–responses were developed for pruritogens. Mice were pretreated with nalbuphine (0.3–10 mg/kg) and then a submaximal dose of pruritogens were administered and the number of scratching bouts was counted. To study if the antiscratch effect of nalbuphine is produced via KOR, we used KOR knock out mice and pharmacologic inhibition of KORs using nor-binaltorphimine, a KOR antagonist. For this aim, we used CQ as a pruritogen. We found that: (a) TAT-HIV-1 protein elicits scratching in a dose-dependent manner; (b) nalbuphine inhibits scratching induced by TAT-HIV-1, DCA, and CQ dose-dependently; and (c) nalbuphine inhibits scratching induced by CQ through KORs. In conclusion, nalbuphine inhibits scratching elicited by multiple pruritogens.

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